We analysed 50 gastric carcinomas (GCs) to verify whether mutations at coding repeats were associated with microsatellite instability (MSI), The tumors included: ten cases with no MSI, 14 cases with MSI=1 locus, 13 cases with MSI=two loci and 13 cases with MSI greater than or equal to 3 loci, We investigated coding repeats within the TGF-beta RII, IGFIIR, BAX, hMSH6, AMSH3 and BRCA2 genes. The TGF-beta RII, IGIIR, BAX, hMSH6 and hMSH3 repeats were altered in 11 (22%), five (10%), four (8%), 16 (32%) and five (10%) cases respectively. Mutations occurred only in MSI-positive (MSI+) tumors and correlated with increasing MSI levels. No alterations of the BRCA2 repeat were found. Mutations in genes other than hMSH6 were strongly associated to kMSH6 mutations, suggesting a key role of this gene. The non-coding BAT-26 and E-Cadherin 3' UTR poly(A)8/(T)15 repeats were analysed in 44 of the 50 cases. Novel tumor-associated alleles were observed only in MSI-positive GCs and were in most cases associated with mutations at coding repeats. Further investigations with BAT-40 confirmed that four cases manifested mononucleotide repeat alterations restricted to hMSH6 and one case to TGF-beta XII. A subset of tumors,vith MSI at two or more dinucleotide loci resulted negative for mutations at coding and non-coding mononucleotide repeats